Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Effect of Modification Protocols on the Effectiveness of Gold Nanoparticles as Drug Delivery Vehicles for Killing of Breast Cancer Cells*

Zahrah Alhalili A C , Daniela Figueroa B C , Martin R. Johnston A , Joe Shapter A D and Barbara Sanderson B
+ Author Affiliations
- Author Affiliations

A Flinders Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Adelaide, SA 5001, Australia.

B Medical Biotechnology, School of Medicine, Flinders University, Adelaide, SA 5001, Australia.

C These two authors contributed equally to this work.

D Corresponding author. Email: joe.shapter@flinders.edu.au

Australian Journal of Chemistry 69(12) 1402-1412 https://doi.org/10.1071/CH16430
Submitted: 22 July 2016  Accepted: 5 September 2016   Published: 6 October 2016

Abstract

The current study evaluated the potential of gold nanoparticles (AuNPs) for the delivery of Taxol to breast cancer cells (T47D) using an in vitro cell culture model. For this study, new loading approaches and novel chemical attachments were investigated. Five different gold nanoparticle-based complexes were used to determine their cytotoxicity towards T47D cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. There was no significant decrease (P > 0.05) in cell viability when T47D cells were treated with AuNPs that did not contain Taxol. However, cells were significantly killed by gold nanoparticles chemically conjugated to Taxol using three different approaches and one novel hybrid AuNP-Taxol nanoparticle, wherein no chemical bonds were involved. These Taxol-loaded AuNPs were more effective at inducing cell death in vitro than a solution of free Taxol used to treat cells. This result demonstrated that Taxol could be released from the particles in the cell culture media for subsequent therapeutic action. Additionally, the experiments proved that the Taxol-loaded AuNPs were more toxic in a dose dependent manner than Taxol as a formulation for the treatment of breast cancer cells. The results of this study suggest that gold nanoparticles have potential for the efficient delivery of Taxol to breast cancer cells. This could provide a future solution as an alternative application method to overcome adverse side effects resulting from current high-dose treatment regimes.


References

[1]  C. DeSantis, J. Ma, L. Bryan, A. Jemal, Ca-Cancer J. Clin. 2014, 64, 52.
         | Crossref | GoogleScholarGoogle Scholar | 24114568PubMed |

[2]  T. J. Key, P. K. Verkasalo, E. Banks, Lancet Oncol. 2001, 2, 133.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD387ntFelsw%3D%3D&md5=cf6f2102fd71533b5da9970326532c21CAS | 11902563PubMed |

[3]  S. Kamer, B. Atasoy, in Principles and Practice of Modern Radiotherapy Techniques in Breast Cancer (Eds A. Haydaroglu, G. Ozyigit) 2013, pp. 19–57 (Springer: New York, NY).

[4]  H. A. Gezairy, in EMRO Technical Publications Series 31 (Ed. WHO) 2006, pp. 1–55 (WHO: Cairo).

[5]  S. B. Pehlivan, Pharm. Res. 2013, 30, 2499.
         | Crossref | GoogleScholarGoogle Scholar | 23959851PubMed |

[6]  H. Laroui, P. Rakhya, B. Xiao, E. Viennois, D. Merlin, Dig. Liver Dis. 2013, 45, 995.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXntFahtbs%3D&md5=18fcaec0c1736e456461a87897711bbbCAS | 23660079PubMed |

[7]  X. Wang, L. Yang, Z. Chen, D. M. Shin, Ca-Cancer J. Clin. 2008, 58, 97.
         | Crossref | GoogleScholarGoogle Scholar | 18227410PubMed |

[8]  R. M. Navalakhe, T. D. Nandedkar, Indian J. Exp. Biol. 2007, 45, 160.
         | 1:CAS:528:DC%2BD2sXjtFCgt78%3D&md5=7f50f0ba49e070b1905ffc540291e28bCAS | 17375555PubMed |

[9]  S. Sagnella, C. Drummond, Aust. Biochem. 2012, 43, 5.

[10]  H. Heiati, R. Tawashi, R. R. Shivers, N. C. Phillips, Int. J. Pharm. 1997, 146, 123.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhtlyrtL4%3D&md5=ff01c6ac7d6b5fa9b3a876741917d732CAS |

[11]  N. Martinho, C. Damge, C. P. Reis, J. Biomater. Nanobiotechnol. 2011, 2, 510.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XlvFSltbk%3D&md5=bc0d2045334986d7c5e8f8a08d35117fCAS |

[12]  A. S. Wahajuddin, Int. J. Nanomedicine 2012, 7, 3445.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVKkurjE&md5=acebd7847fd0c305c4d16f9af2e3cc7eCAS |

[13]  L. Qi, X. Gao, Expert Opin. Drug Delivery 2008, 5, 263.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXislKjtrg%3D&md5=ff074b654f7fc4a0bd8f293c7d736ad9CAS |

[14]  S. Jain, D. G. Hirst, J. M. O’Sullivan, Br. J. Radiol. 2012, 85, 101.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC383gtFOlsw%3D%3D&md5=41461f9a169f57b14891d164b6f982bfCAS | 22010024PubMed |

[15]  A. M. Alkilany, C. J. Murphy, Langmuir 2009, 25, 13874.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXms1KntLY%3D&md5=22da1ca3555f2f126d3a3f85956e3d21CAS | 20560552PubMed |

[16]  C. M. Goodman, C. D. McCusker, T. Yilmaz, V. M. Rotello, Bioconjugate Chem. 2004, 15, 897.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXksFelur4%3D&md5=704f207bf1e69e04b3eae8b20df8f5a7CAS |

[17]  Y. Pan, A. Leifert, D. Ruau, S. Neuss, J. Bornemann, G. Schmid, W. Brandau, U. Simon, W. Jahnen-Dechent, Small 2009, 5, 2067.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFGktrvK&md5=236985b6134e8e5fdd684d257473692aCAS | 19642089PubMed |

[18]  Y. Ding, Y.-Y. Zhou, H. Chen, D.-D. Geng, D.-Y. Wu, J. Hong, W.-B. Shen, T.-J. Hang, C. Zhang, Biomaterials 2013, 34, 10217.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVynur%2FO&md5=ce1f6f49433d6cd1a978edf0644e1fcbCAS | 24055524PubMed |

[19]  J. Xu, L. Ma, Y. Liu, F. Xu, J. Nie, G. Ma, Int. J. Biol. Macromol. 2012, 50, 438.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsF2nurw%3D&md5=f341231f71464540c227b59fdd0bd6b9CAS | 22230611PubMed |

[20]  D. Yang, S. Van, X. Jiang, L. Yu, Int. J. Nanomedicine 2011, 6, 85.
         | 1:CAS:528:DC%2BC3MXht1Oht70%3D&md5=e058aa3f0319999dd9e1668971c9d52dCAS | 21289985PubMed |

[21]  G. I. Harisa, M. F. Ibrahim, F. Alanazi, G. A. Shazly, Saudi Pharm. J. 2014, 22, 223.
         | Crossref | GoogleScholarGoogle Scholar | 25061408PubMed |

[22]  A. Brufsky, K. Hoelzer, T. Beck, R. Whorf, M. Keaton, P. Nadella, E. Krill-Jackson, J. Kroener, E. Middleman, M. Frontiera, D. Paul, T. Panella, J. Bromund, L. Zhao, M. Orlando, F. Tai, M. D. Marciniak, C. Obasaju, J. Hainsworth, Clin. Breast Cancer 2011, 11, 211.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlKisr%2FO&md5=3d149bd4d6c9073409ef9c7967eb1766CAS | 21723792PubMed |

[23]  N. Larson, J. Yang, A. Ray, D. L. Cheney, H. Ghandehari, J. Kopeček, Int. J. Pharm. 2013, 454, 435.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtFOrsLjL&md5=1cb4317dda8e8bbebdfa2f3c88f3b97fCAS | 23827653PubMed |

[24]  Z.-Z. Lin, C. Hsu, Y.-C. Chang, C.-J. Yu, C.-H. Hsu, C.-C. Lin, A.-L. Cheng, P.-C. Yang, C.-H. Yang, Lung Cancer 2008, 60, 215.
         | Crossref | GoogleScholarGoogle Scholar | 18022277PubMed |

[25]  D. N. Heo, D. H. Yang, H.-J. Moon, J. B. Lee, M. S. Bae, S. C. Lee, W. J. Lee, I.-C. Sun, I. K. Kwon, Biomaterials 2012, 33, 856.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVyksb%2FE&md5=5e15ee08051da345e182781436087f33CAS | 22036101PubMed |

[26]  C. Wang, Y. Wang, Y. Wang, M. Fan, F. Luo, Z. Qian, Int. J. Pharm. 2011, 414, 251.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnvFOkur4%3D&md5=1a83769d29a319492d3a4aa482d53736CAS | 21596124PubMed |

[27]  W. J. Gradishar, S. Tjulandin, N. Davidson, H. Shaw, N. Desai, P. Bhar, M. Hawkins, J. O’Shaughnessy, J. Clin. Oncol. 2005, 23, 7794.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht1Cqs7nK&md5=6482a8cdd3bb2ac1074129ac4a6fae8aCAS | 16172456PubMed |

[28]  P. M. Tiwari, K. Vig, V. A. Dennis, S. R. Singh, Nanomaterials 2011, 1, 31.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1WrsLjI&md5=654c702a627f2d5262fe456f729a0301CAS |

[29]  K. Knop, R. Hoogenboom, D. Fischer, U. S. Schubert, Angew. Chem., Int. Ed. 2010, 49, 6288.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVOqtLbN&md5=09a1ddd5aaadd9b2d8fa34e04d5a239dCAS |

[30]  S. Takae, Y. Akiyama, H. Otsuka, T. Nakamura, Y. Nagasaki, K. Kataoka, Biomacromolecules 2005, 6, 818.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlsFCgtg%3D%3D&md5=ac46f2085e809d088883a097412a1f33CAS | 15762646PubMed |

[31]  H. Otsuka, Y. Akiyama, Y. Nagasaki, K. Kataoka, J. Am. Chem. Soc. 2001, 123, 8226.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlsFygtLg%3D&md5=0b4b3e8a2367be9dd356701f79d99e9eCAS | 11516273PubMed |

[32]  R. G. Shimmin, A. B. Schoch, P. V. Braun, Langmuir 2004, 20, 5613.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktlajtLs%3D&md5=d0918cf5af897d79b60276597be51381CAS | 15986709PubMed |

[33]  J. D. Gibson, B. P. Khanal, E. R. Zubarev, J. Am. Chem. Soc. 2007, 129, 11653.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpsVeksLw%3D&md5=b2b15d0924430088a60baf144313f69dCAS | 17718495PubMed |

[34]  O. Biondi, S. Motta, P. Mosesso, Mutagenesis 2002, 17, 261.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XktFSnur8%3D&md5=d90ff9b2c579a0576176c741dd727be5CAS | 11971999PubMed |

[35]  T. Ganesh, Bioorg. Med. Chem. 2007, 15, 3597.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXkslCitrs%3D&md5=d5da79bc1fa1504053ce390898a4ba5bCAS | 17419065PubMed |

[36]  J. R. Hwu, Y. S. Lin, T. Josephrajan, M.-H. Hsu, F.-Y. Cheng, C.-S. Yeh, W.-C. Su, D.-B. Shieh, J. Am. Chem. Soc. 2009, 131, 66.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFSjtb%2FI&md5=b8292a5748224ab0dba3f19c6f0e6b3dCAS | 19072111PubMed |

[37]  F. Everaerts, M. Torrianni, M. Hendriks, J. Feijen, J. Biomed. Mater. Res., Part A 2008, 85A, 547.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXkslyiuro%3D&md5=13c95991a6ac9347d251d39c0a9a2048CAS |

[38]  B. J. S. Sanderson, R. Lam, J. Alharthi, J. Shapter, Procedia Eng. 2014, 92, 26.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtVKltbo%3D&md5=e9a2d615a05fd4fc2167df82cc499c1eCAS |

[39]  K. C. Grabar, R. G. Freeman, M. B. Hommer, M. J. Natan, Anal. Chem. 1995, 67, 735.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXjt1Sitbg%3D&md5=b24682e9d129a5c080316596ec89d5abCAS |

[40]  J. Turkevich, P. C. Stevenson, J. Hillier, Discuss. Faraday Soc. 1951, 11, 55.
         | Crossref | GoogleScholarGoogle Scholar |

[41]  S.-Y. Lin, Y.-T. Tsai, C.-C. Chen, C.-M. Lin, C.-h. Chen, J. Phys. Chem. B 2004, 108, 2134.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXls1WrsA%3D%3D&md5=52ecd61bd38b7d479421ac8a1ca09e99CAS |

[42]  D. Li, Q. He, Y. Cui, L. Duan, J. Li, Biochem. Biophys. Res. Commun. 2007, 355, 488.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitFOlsb8%3D&md5=3c6902694d132d8dc57ef31f688e1eb8CAS | 17306226PubMed |

[43]  J.-Z. Chen, S. V. Ranade, X.-Q. Xie, Int. J. Pharm. 2005, 305, 129.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFOhtbfP&md5=7c96a9bc63a1eb75545f6bac51a0ce77CAS | 16207518PubMed |

[44]  J. Conde, A. Ambrosone, V. Sanz, Y. Hernandez, V. Marchesano, F. Tian, H. Child, C. C. Berry, M. R. Ibarra, P. V. Baptista, C. Tortiglione, J. M. de la Fuente, ACS Nano 2012, 6, 8316.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFyqtb7O&md5=51e23e8259bc74d6727202898b77f2b0CAS | 22882598PubMed |

[45]  G. P. Huang, S. Shanmugasundaram, P. Masih, D. Pandya, S. Amara, G. Collins, T. L. Arinzeh, J. Biomed. Mater. Res. A 2015, 103, 762.
         | Crossref | GoogleScholarGoogle Scholar | 24828818PubMed |

[46]  F. Everaerts, M. Torrianni, M. Hendriks, J. Feijen, J. Biomed. Mater. Res., Part A 2008, 85A, 547.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXkslyiuro%3D&md5=13c95991a6ac9347d251d39c0a9a2048CAS |

[47]  S. Rudershausen, C. Grüttner, M. Frank, J. Teller, F. Westphal, Eur. Cells Mater. 2002, 3, 81–3.

[48]  H. Gréen, K. Vretenbrant, B. Norlander, C. Peterson, Rapid Commun. Mass Spectrom. 2006, 20, 2183.
         | Crossref | GoogleScholarGoogle Scholar | 16791868PubMed |

[49]  X. Liu, M. Atwater, J. Wang, Q. Huo, Colloids Surf., B 2007, 58, 3.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlvVOksr0%3D&md5=f9b7c9c98fdb2214e4ab83bacc480158CAS |

[50]  T. Mosmann, J. Immunol. Methods 1983, 65, 55.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c%2FovFSmtw%3D%3D&md5=00f21a2f65c986bb8976bb08945c8988CAS | 6606682PubMed |

[51]  A. Kroll, M. H. Pillukat, D. Hahn, J. Schnekenburger, Eur. J. Pharm. Biopharm. 2009, 72, 370.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmtVOjtbk%3D&md5=90df69852434457103d10eb5005eaeceCAS | 18775492PubMed |

[52]  M. V. Berridge, P. M. Herst, A. S. Tan, Biotechnol. Annu. Rev. 2005, 11, 127.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVCjsrY%3D&md5=5ad97de211387eebcbff0159987423bbCAS | 16216776PubMed |

[53]  S. M. Hussain, K. L. Hess, J. M. Gearhart, K. T. Geiss, J. J. Schlager, Toxicol. In Vitro 2005, 19, 975.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFOhtLnE&md5=2179543c32145a41bce97d0ce6858907CAS | 16125895PubMed |

[54]  C. M. Sayes, K. L. Reed, D. B. Warheit, Toxicol. Sci. 2007, 97, 163.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlvVKjtL4%3D&md5=1151e8fe308b4e60c1016a316ce9f2eaCAS | 17301066PubMed |

[55]  M. R. Wilson, V. Stone, R. T. Cullen, A. Searl, R. L. Maynard, K. Donaldson, Occup. Environ. Med. 2000, 57, 727.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXotFSiur8%3D&md5=fbbff643a991f4ba6cba88e4c95d9b4bCAS | 11024195PubMed |

[56]  D. Granchi, G. Ciapetti, L. Savarino, D. Cavedagna, M. E. Donati, A. Pizzoferrato, J. Biomed. Mater. Res. 1996, 31, 183.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XisFeltro%3D&md5=49ffee4ddcacafff4fa39e83a025681dCAS | 8731206PubMed |

[57]  L. Belyanskaya, P. Manser, P. Spohn, A. Bruinink, P. Wick, Carbon 2007, 45, 2643.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1ShtL7K&md5=a2d8e46da10f99bf108c6de376f6e0e1CAS |

[58]  R. R. Davis, P. E. Lockwood, D. T. Hobbs, R. L. W. Messer, R. J. Price, J. B. Lewis, J. C. Wataha, J. Biomed. Mater. Res., Part B 2007, 83B, 505.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1ynsLzF&md5=540cd00cfb6905f42d9d0a32fdfe7e7fCAS |

[59]  E. E. Connor, J. Mwamuka, A. Gole, C. J. Murphy, M. D. Wyatt, Small 2005, 1, 325.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhsVaiu74%3D&md5=63a1f7891bbdd685b5f6c8d0dc3ba623CAS | 17193451PubMed |

[60]  E. C. Cho, Y. Liu, Y. Xia, Angew. Chem., Int. Ed. 2010, 49, 1976.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjtFSnsL0%3D&md5=95c4b27b0860bd75bcd64e95b41ff0f7CAS |

[61]  S. K. Dordunoo, H. M. Burt, Int. J. Pharm. 1996, 133, 191.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xjt1Sntbw%3D&md5=37fc6c103412cee2b40c6b1eb9e16142CAS |